Immune Surveillance of the CNS following Infection and Injury

The central nervous system (CNS) contains a sophisticated neural network that must be constantly surveyed in order to detect and mitigate a diverse array of challenges. The innate and adaptive immune systems actively participate in this surveillance, which is critical for the maintenance of CNS homeostasis and can facilitate the resolution of infections, degeneration, and tissue damage. Infections and sterile injuries represent two common challenges imposed on the CNS that require a prompt immune response. While the inducers of these two challenges differ in origin, the resultant responses orchestrated by the CNS share some overlapping features. Here, we review how the CNS immunologically discriminates between pathogens and sterile injuries, mobilizes an immune reaction, and, ultimately, regulates local and peripherally-derived immune cells to provide a supportive milieu for tissue repair.

TrendsSpecialized innate immune sentinels inhabit the CNS lining and parenchyma, and are usually among the first responders to infections and sterile injuries. Aided by infiltrating cells, the innate immune system orchestrates both the inflammatory and reparative phases of CNS infections/injuries.Effector T cells recruited to the CNS can cause severe pathology; however, therapeutic antiviral T cells can purge a persistent infection from microglia without causing cellular damage, and bystander CD4+ T cells can mediate neuroprotection in an MHC II-independent manner following spinal cord injury.CNS-infiltrating monocytes can injure barrier structures or promote wound healing, depending on their state of differentiation and route of CNS entry.Innate and adaptive immune cells operating in the infected or injured CNS are heavily regulated to limit immunopathology and promote tissue repair.